Mitral valve transcriptome analysis in thirty-four age-matched Cavalier King Charles Spaniels with or without myxomatous mitral valve disease

AbstractWe here report the results of a mitral valve transcriptome study designed to identify genes and molecular pathways involved in development of myxomatous mitral valve disease (MMVD) in dogs. The study is focused on a cohort of elderly age-matched dogs (n=34, age ~10 years) from a single breed – Cavalier King Charles Spaniels – with a high incidence of MMVD. The cohort comprises 19 dogs (10♀, 9♂) without MMVD, or with early stages of MMVD, and 15 dogs (6♀, 9♂) with congestive heart failure caused by MMVD. I.e. we compare gene expression in breed and age matched groups of dogs, which only differ with respect to severity of disease. We identify 56 genes, which are differentially expressed between the two groups. In this list of genes, we confirm an enrichment of genes related to the TNFβ signaling pathway, extracellular matrix organization, vascular development, and endothelium damage, which also have been identified in previous studies. However, the genes with the greatest difference in expression between the two groups areCNTN3andMYH1. Both genes encode proteins, which are predicted to have an effect on the contractile activity of myocardial cells, which in turn may have an effect on valvular performance and hemodynamics across the mitral valve. This may result in shear forces with impact on MMVD progression.